During the late 1950s and early 1960s, thalidomide was sold as a sedative in over 40 countries and was often prescribed to pregnant women as a treatment for morning sickness. Before its teratogenic activity came to light and its use was discontinued, it was estimated that several thousands to ten thousands or more birth defects (malformation), including stillbirth, had occurred (Cited Literatures 1 to 3). Use of thalidomide by women in their third to eighth week of pregnancy causes birth defects such as limb, ear, cardiac, and gastrointestinal malformations, which are called thalidomide embryopathy (Cited Literatures 1 to 3). In particular, limb and ear malformations are frequent. The limb malformation, known as phocomelia, is characterized by shortening of legs and arms. The ear malformations are represented by anotia, microtia, and hearing loss. Despite considerable effort for determination of causes, little is known about how these developmental defects are induced. Previous studies have suggested thalidomide-induced oxidative stress and its anti-angiogenic action as a possible cause of teratogenicity (Cited Literatures 4 and 5). However, several important questions remain unanswered, such as what molecules are direct targets of thalidomide and how the target factors mediate the thalidomide-induced teratogenicity.
Meanwhile, a protein called CRBN is known as a candidate causative factor for mild mental retardation in humans (Non-Patent Document 1 and Cited Literature 11). While this protein has also been reported to bind to a protein called Damaged DNA Binding protein 1 (DDB1) (Non-Patent Document 2 and Cited Literature 12), its relationship with thalidomide has never been reported.